ATE523194T1 - Bis(thiohydrazidamide) in kombination mit taxol für die behandlung von krebs - Google Patents
Bis(thiohydrazidamide) in kombination mit taxol für die behandlung von krebsInfo
- Publication number
- ATE523194T1 ATE523194T1 AT09004577T AT09004577T ATE523194T1 AT E523194 T1 ATE523194 T1 AT E523194T1 AT 09004577 T AT09004577 T AT 09004577T AT 09004577 T AT09004577 T AT 09004577T AT E523194 T1 ATE523194 T1 AT E523194T1
- Authority
- AT
- Austria
- Prior art keywords
- treatment
- cancer
- paclitaxel
- thiohydrazidamide
- taxol
- Prior art date
Links
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D307/68—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C327/00—Thiocarboxylic acids
- C07C327/38—Amides of thiocarboxylic acids
- C07C327/56—Amides of thiocarboxylic acids having nitrogen atoms of thiocarboxamide groups further bound to another hetero atom
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- A—HUMAN NECESSITIES
- A45—HAND OR TRAVELLING ARTICLES
- A45D—HAIRDRESSING OR SHAVING EQUIPMENT; EQUIPMENT FOR COSMETICS OR COSMETIC TREATMENTS, e.g. FOR MANICURING OR PEDICURING
- A45D8/00—Hair-holding devices; Accessories therefor
- A45D8/004—Hair-holding devices; Accessories therefor with decorative arrangements or form
- A45D8/006—Interchangeable ornaments attached to hair holding devices
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/337—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/58—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. poly[meth]acrylate, polyacrylamide, polystyrene, polyvinylpyrrolidone, polyvinylalcohol or polystyrene sulfonic acid resin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/44—Iso-indoles; Hydrogenated iso-indoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/83—Thioacids; Thioesters; Thioamides; Thioimides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
- C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
- C07D261/10—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D261/18—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D333/38—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D333/52—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes
- C07D333/62—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the hetero ring
- C07D333/68—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/04—Systems containing only non-condensed rings with a four-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
- C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epoxy Compounds (AREA)
- Indole Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyridine Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US30425201P | 2001-07-10 | 2001-07-10 | |
US36193602P | 2002-03-06 | 2002-03-06 |
Publications (1)
Publication Number | Publication Date |
---|---|
ATE523194T1 true ATE523194T1 (de) | 2011-09-15 |
Family
ID=26973914
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
AT09004577T ATE523194T1 (de) | 2001-07-10 | 2002-07-10 | Bis(thiohydrazidamide) in kombination mit taxol für die behandlung von krebs |
AT02752238T ATE448199T1 (de) | 2001-07-10 | 2002-07-10 | Verbindungen mit taxol-verstärkender wirkung |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
AT02752238T ATE448199T1 (de) | 2001-07-10 | 2002-07-10 | Verbindungen mit taxol-verstärkender wirkung |
Country Status (20)
Country | Link |
---|---|
US (4) | US6762204B2 (cs) |
EP (2) | EP1406870B1 (cs) |
JP (1) | JP4344234B2 (cs) |
KR (2) | KR101092139B1 (cs) |
CN (1) | CN1308302C (cs) |
AT (2) | ATE523194T1 (cs) |
AU (1) | AU2002354641B2 (cs) |
BR (1) | BR0211228A (cs) |
CA (1) | CA2454120C (cs) |
DE (1) | DE60234345D1 (cs) |
ES (1) | ES2395141T3 (cs) |
HK (1) | HK1060117A1 (cs) |
IL (2) | IL159772A0 (cs) |
IS (1) | IS2718B (cs) |
MX (1) | MXPA04000243A (cs) |
NO (1) | NO333230B1 (cs) |
NZ (1) | NZ530964A (cs) |
TW (1) | TWI297335B (cs) |
WO (1) | WO2003006428A1 (cs) |
ZA (1) | ZA200401054B (cs) |
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TWI297335B (en) * | 2001-07-10 | 2008-06-01 | Synta Pharmaceuticals Corp | Taxol enhancer compounds |
US6924312B2 (en) * | 2001-07-10 | 2005-08-02 | Synta Pharmaceuticals Corp. | Taxol enhancer compounds |
TWI252847B (en) * | 2001-07-10 | 2006-04-11 | Synta Pharmaceuticals Corp | Synthesis of taxol enhancers |
TWI332943B (en) * | 2001-07-10 | 2010-11-11 | Synta Pharmaceuticals Corp | Taxol enhancer compounds |
HUP0500843A2 (hu) * | 2001-12-20 | 2005-12-28 | Bristol-Myers Squibb Co., | Fokozott biológiai hasznosulású, szájon át hatásos taxánszármazékokat tartalmazó gyógyszerkészítmények |
AU2006228035B2 (en) * | 2003-01-15 | 2010-02-18 | Synta Pharmaceuticals Corp. | Bis (thio-hydrazide amide) compounds for treating multi-drug resistant cancer |
TWI330079B (en) * | 2003-01-15 | 2010-09-11 | Synta Pharmaceuticals Corp | Treatment for cancers |
ME01644B (me) * | 2004-06-23 | 2014-09-20 | Synta Pharmaceuticals Corp | BIS(TIO-HIDRAZID AMIDNE) SOLl ZA TRETMAN KANCERA |
US20060167106A1 (en) * | 2004-11-19 | 2006-07-27 | Mei Zhang | Compounds acting at the centrosome |
CA2587598A1 (en) * | 2004-11-19 | 2006-05-26 | Synta Pharmaceuticals Corp. | Bis(thio-hydrazide amides) for increasing hsp70 expression |
AU2005232302B2 (en) | 2005-02-14 | 2011-08-18 | Konami Australia Pty Ltd | Gaming Machine with runs of symbols |
CA2603314A1 (en) * | 2005-04-15 | 2006-10-26 | Synta Pharmaceuticals Corp. | Methods of increasing natural killer cell activity for therapy |
WO2006113493A2 (en) * | 2005-04-15 | 2006-10-26 | Synta Pharmaceuticals Corp. | Methods of determining cancer prognosis via natural killer cell activity |
CA2604907A1 (en) | 2005-04-15 | 2006-10-26 | Synta Pharmaceuticals Corp. | Combination cancer therapy with bis(thiohydrazide) amide compounds |
CN101223133B (zh) * | 2005-05-16 | 2012-02-29 | 辛塔制药公司 | 双(硫代酰肼酰胺)盐的合成 |
RU2433822C2 (ru) * | 2005-08-16 | 2011-11-20 | Синта Фармасьютиклз Корп. | Композиция бис(тио-гидразид амида) |
EP2063878A2 (en) * | 2006-08-21 | 2009-06-03 | Synta Pharmaceuticals Corporation | Bis(thiohydrazide amides) for use in preventing or delaying the recurrence of melanoma |
EP2061451A2 (en) * | 2006-08-21 | 2009-05-27 | Synta Pharmaceuticals Corporation | Bis(thiohydrazide amides) for treating melanoma |
US8785451B2 (en) * | 2006-08-21 | 2014-07-22 | Synta Pharmaceuticals Corp. | Compounds for the treatment of proliferative disorders |
AU2007288338B2 (en) | 2006-08-21 | 2012-05-03 | Synta Pharmaceuticals Corp. | Compounds for treating proliferative disorders |
EP2059236A2 (en) * | 2006-08-21 | 2009-05-20 | Synta Pharmaceuticals Corporation | Combination with bis(thiohydrazide amides) for treating cancer |
US8497272B2 (en) | 2006-08-21 | 2013-07-30 | Synta Pharmaceuticals Corp. | Compounds for treating proliferative disorders |
EP2076254A2 (en) * | 2006-08-31 | 2009-07-08 | Synta Pharmaceuticals Corporation | Combination with bis(thiohydrazide amides) for treating cancer |
US9498528B2 (en) * | 2006-09-13 | 2016-11-22 | Genzyme Corporation | Treatment of multiple sclerosis (MS) |
TW200829543A (en) * | 2006-09-15 | 2008-07-16 | Synta Pharmaceuticals Corp | Purification of bis(thiohydrazide amides) |
WO2009020631A2 (en) | 2007-08-07 | 2009-02-12 | Synta Pharmaceuticals Corp. | Compounds for treating proliferative disorders |
WO2009064374A2 (en) * | 2007-11-09 | 2009-05-22 | Synta Pharmaceuticals Corp. | Oral formulations of bis(thiohydrazide amides) |
US8581004B2 (en) | 2008-02-21 | 2013-11-12 | Synta Pharmaceuticals Corp. | Compounds for treating proliferative disorders |
US8633323B2 (en) * | 2008-03-31 | 2014-01-21 | Synta Pharmaceuticals Corp. | Process for preparing bis(thiohydrazide amides) |
CN102256937B (zh) | 2008-10-22 | 2014-12-17 | 辛塔医药品有限公司 | 双[硫代酰肼酰胺]化合物的过渡金属络合物 |
EP2373624A4 (en) | 2008-10-22 | 2014-06-11 | Synta Pharmaceuticals Corp | TRANSITION METAL COMPLEXES OF A TO [THIOHYDRAZIDAMID] COMPOUND |
US8525776B2 (en) * | 2008-10-27 | 2013-09-03 | Lenovo (Singapore) Pte. Ltd | Techniques for controlling operation of a device with a virtual touchscreen |
CA2745065A1 (en) | 2008-12-01 | 2010-06-10 | Synta Pharmaceuticals Corp. | Compounds for treating proliferative disorders |
WO2011069159A2 (en) | 2009-12-04 | 2011-06-09 | Synta Pharmaceuticals Corp. | Bis[thiohydrazide amide] compounds for treating leukemia |
US8815945B2 (en) | 2010-04-20 | 2014-08-26 | Masazumi Nagai | Use of bis [thiohydrazide amide] compounds such as elesclomol for treating cancers |
JP2014534238A (ja) | 2011-11-10 | 2014-12-18 | シンタ ファーマシューティカルズ コーポレーション | 癌を治療するためのビス(チオヒドラジドアミド)化合物の投与 |
US20130149392A1 (en) | 2011-12-12 | 2013-06-13 | Synta Pharmaceuticals Corp. | Method of treating non-small cell lung cancer with bis-(thiohydrazide)amide compounds |
WO2013103795A1 (en) | 2012-01-05 | 2013-07-11 | The Board Of Trustees Of The Leland Stanford Junior University | Bis (thiohydrazide amide) compounds for treating cancers |
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